Alpers Disease - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Alpers disease is a progressive and severe disorder. It is found to occur in one in every 100,000 individuals. Both males and females are equally affected. The symptoms of Alpers disease are not present at the time of birth. However, symptoms develop at three months or between 2 to 25 years.

What Is Alpers Disease?

Alpers disease is an inherited condition that affects the energy units (mitochondria) of all the cells in the body. Thereby causing brain, liver, and muscle abnormalities. The liver symptoms may get complicated in a few patients, requiring early management. It is also referred to as Alpers-Huttenlocher syndrome and progressive infantile poliodystrophy.

What Causes Alpers Disease?

• Genetic changes (mutations) that occur in the POLG gene are found to cause Alpers syndrome. The POLG gene is responsible for the multiplication and repair of mitochondrial DNA (a small chromosome found inside the mitochondria). Any mutation in the POLG gene causes defective mitochondrial DNA, which produces less energy. It affects the brain, liver, and muscles which generally need more power to function at their best. When the child acquires the abnormal and defective POLG gene from both the mother and father, it causes Alpers syndrome. If the child receives one normal gene from one parent and a faulty gene from the other, the child remains a carrier of the disease and does not show any symptoms.

• Some researchers have found that a viral infection may be responsible for genetic changes in the mitochondrial DNA.

• Certain drugs like Valproic acid are also found to speed up the symptoms of Alpers disease.

What Are the Symptoms of Alpers Disease?

The classical features of the Alpers disease are as follows:

• Uncontrollable seizures occur due to abnormal brain activity, and it develops at the early age of between 3 months to 5 years.

• Intellectual functions like thinking, remembering, and reasoning slow down and impair (dementia).

• The muscle tone or strength decreases (hypotonia).

• Jerking of muscles is also observed.

• Liver abnormalities.

The Other Clinical Features Include:

• Decrease in the coordination of muscular activities.

• Stiffness of muscles occurs.

• Reduction in the level of blood glucose (hypoglycemia).

• The abnormalities of the liver progress to severe scarring (cirrhosis) and damage, eventually leading to liver failure.

• In a few patients, damage to the optic nerve (optic atrophy) that supplies visual information to the brain happens, leading to blindness.

• Other gastrointestinal disorders cause swallowing difficulties.

• The level of intelligence is lowered than the actual level in normal individuals.

• The movements of arms and legs are uncontrollable.

• Lack of ability to gain proper weight and height.

• Infections may cause brain disease (encephalopathy).

• Diseases that affect the heart muscle (cardiomyopathy) are seen in the later stage of Alpers syndrome.

• Headache, anxiety, and depression are a few other symptoms.

How Is Alpers Disease Diagnosed?

• Alpers disease can be diagnosed in children by physical examination, detailed medical and family history, and other laboratory examinations.

• Magnetic Resonance Imaging (MRI) is ordered to detect the abnormalities of brain structures like atrophy. In patients with Alpers disease, the MRI findings show an increased volume of gray matter. The brain's gray matter contains more functional units (neurons) responsible for controlling muscle activities, memory, etc.

• Cerebrospinal Fluid Analysis is a procedure of inserting a needle in the lower portion of the spine to collect the fluid (spinal tap) and send it for laboratory examination. Cerebrospinal fluid covers and protects the brain within the skull and contains proteins, sugars, and other chemicals. The cerebrospinal fluid analysis shows increased protein levels in patients with Alpers disease.

• Electroencephalogram (EEG) measures the brain's activities and diagnoses seizures.

• Genetic Testing is done to detect the mutations in the POLG gene that cause mitochondrial deficiency.

What Is the Differential Diagnosis?

The various diseases that have similar features to Alpers disease are:

• Myoclonic Epilepsy is an inherited disorder, and the symptoms develop at the age of 6. The signs include an increase in the severity of seizures and loss of memory and thinking abilities. Loss of consciousness also occurs during the initial stage of attacks.

• Batten Disease occurs due to the accumulation of harmful fats in the body's cells. The clinical features include defects in the optic nerve, seizures, decreased intellectual levels, lack of muscle coordination, and other spinal abnormalities.

• Leigh's Disease is a genetic disease that affects the optic nerve, brain, and spinal cord. The symptoms in the early infancy lead to growth and developmental disturbances, lack of muscular coordination, enlarged heart, and vision problems in the later stage of the disease.

• Tay-Sachs Disease affects the brain, spinal cord, and other nerves. It is characterized by vision problems, feeding difficulties, loss of muscular coordination, etc. The symptoms are not present during birth and may develop in infancy.

How Is Alpers Disease Treated?

Alpers Disease poses a significant challenge for doctors to treat. However, the symptoms can be reduced by the following methods:

• Anticonvulsant drugs are found helpful in treating seizures. However, Valproic acid is avoided as it progresses liver damage.

• Physical therapy is provided to improve the children's sitting postures and muscle movements.

• Muscle relaxants are suggested to ease the pain and relieve the stiffness of muscles.

• Stress can be reduced by massage therapy.

• To maintain proper nutrition, frequent and small amounts of low protein foods are provided.

• Feeding tubes are placed if there are difficulties in swallowing. Percutaneous endoscopic gastrostomy (PEG) is a procedure of placing a tube into the stomach to supply food.

• Therapies are provided to improve speech and to support in doing daily activities.

• Artificial ventilation is provided to improve breathing.

Conclusion:

Alpers disease is uncommon, and its treatment is quite difficult. However, the joint hands of parents and therapists in early investigation and planning of appropriate management steps help and support the affected children.